# Mechanisms in Blood Clotting

> **NIH NIH R35** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $988,138

## Abstract

Abstract
The overall vision is to achieve a detailed understanding of mechanisms that regulate the blood clotting
system, with a special goal of identifying the aspects of the clotting machinery that function differentially in
hemostasis versus thrombosis. The conceptual framework is that human thrombotic diseases result from an
otherwise protective mechanism (immunothrombosis) gone awry. In this view, hemostasis following vascular
injury is driven by the prompt exposure of blood to preexisting, natural procoagulants such as tissue factor and
collagen that are ubiquitous throughout the body and that induce rapid formation of hemostatic plugs. On the
other hand, immunothrombosis is likely triggered and/or greatly enhanced by the elaboration of damage-
associated molecular patterns (DAMPs) and pathogen-associate molecular patterns (PAMPs). An important
concept is that many of these PAMPs and DAMPs that drive immunothrombosis are potential therapeutic
targets with little or no involvement in normal hemostasis. In order to achieve this vision, we need to have a
much better mechanistic understanding of what regulates blood clotting reactions, and in particular we need to
identify and understand the DAMPs that drive thrombosis and coagulopathies. Work initiated in our laboratory
in the mid-2000s was the first to identify inorganic polyphosphate (polyP) as a DAMP and PAMP with potent
prothrombotic and proinflammatory effects, a finding which opened up a new area of investigation in the field of
hemostasis and thrombosis. The proposed work in this grant will focus on three general areas within the
general conceptual framework outlined above: elucidating mechanisms by which procoagulant anionic
polymers such as polyP and nucleic acids regulate blood clotting, inflammation and fibrosis; identifying key
structural details that control the function of the tissue factor/factor VIIa complex; and achieving a detailed
understanding of how phospholipid bilayers regulate blood clotting reactions. These studies will build on our
prior success in this area and will further advance the field.

## Key facts

- **NIH application ID:** 10785047
- **Project number:** 1R35HL171334-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** James H. Morrissey
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $988,138
- **Award type:** 1
- **Project period:** 2024-03-01 → 2031-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10785047

## Citation

> US National Institutes of Health, RePORTER application 10785047, Mechanisms in Blood Clotting (1R35HL171334-01). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10785047. Licensed CC0.

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